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Gene expression signatures for mESC treated by RNAi strategy on down regulation of gene Mtf2

ABSTRACT: To further explore the function of Mtf2, the homolog of Drosophila Polycomb group gene PCL, we have employed the mouse whole genome microarray expression profiling as a discovery platform to identify genes mediated by Mtf2. Oligos of 2 different RNAi target sites on gene Mtf2 were cloned into RNAi Vector pSuper and transfected individually into Mouse Embryonic Stem Cell line E14. Empty Vector pSuper and plasmid containing RNAi target against gene Luciferase (Firefly) were performed in the same way as negative controls. The down regulation effect of gene Mtf2 was quantified by real-time PCR in the same RNA samples subjected to microarray analysis.

ORGANISM(S): Mus musculus

PROVIDER: GSE18319 | GEO | 2010/02/20

SECONDARY ACCESSION(S): PRJNA117971

REPOSITORIES: GEO

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Gene expression signatures for mESC treated by RNAi strategy on down regulation of gene Mtf2

Project description:To further explore the function of Mtf2, the homolog of Drosophila Polycomb group gene PCL, we have employed the mouse whole genome microarray expression profiling as a discovery platform to identify genes mediated by Mtf2. Oligos of 2 different RNAi target sites on gene Mtf2 were cloned into RNAi Vector pSuper and transfected individually into Mouse Embryonic Stem Cell line E14. Empty Vector pSuper and plasmid containing RNAi target against gene Luciferase (Firefly) were performed in the same way as negative controls. The down regulation effect of gene Mtf2 was quantified by real-time PCR in the same RNA samples subjected to microarray analysis. mESC was transfected by RNAi plasmids with resistence of puromycin and selected by Puromycin(1mg/ml) for 2 days. 4 independent experiments were performed for vector pSuper, plasimd pSuper-Luci-RNAi, pSuper-Mtf2-RNAi-1, pSuper-Mtf2-RNAi-3.

2010-02-20 | E-GEOD-18319 | biostudies-arrayexpress

Mtf2 is a methylation-sensitive DNA-binding recruiter of Polycomb

Project description:Polycomb repression of gene expression is critical for development, with a pivotal role for trimethylation of lysine 27 of histone H3 (H3K27me3) deposited by Polycomb Repressive Complex 2 (PRC2). While the function and regulation of PRC2 have been extensively studied, the mechanism(s) by which it is recruited to specific genomic targets has remained largely elusive, in particular in vertebrates. Here we identify the PRC2-associated protein Mtf2 as a novel DNA methylation-sensitive PRC2 recruiter in mouse embryonic stem cells (mESCs). Mtf2 directly binds to DNA and is essential for recruitment of PRC2 both in vitro and in vivo. Genome-wide recruitment of the PRC2 catalytic subunit Ezh2 to genomic targets is drastically impaired in Mtf2 knock-out mESCs, resulting in largely reduced H3K27me3 deposition. Mtf2 selectively binds regions with high density of closely spaced unmethylated CpG-containing motifs with a locally unwound helical structure. This binding is dependent on one of the Mtf2 PHD domains, a protein domain shared among Pcl homologs, and an Mtf2-specific domain. The sequences bound by Mtf2 are enriched in PRC2-repressed CpG island-containing targets in zebrafish, Xenopus, mouse and human, suggesting that Mtf2-mediated PRC2 recruitment to unmethylated genomic regions is conserved among vertebrates.

2018-05-07 | PXD005821 | Pride

Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis. [ChIP-seq]

Project description:genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2-/- erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions. The resulting de-repression of transcriptional and signaling networks blocks definitive erythroid development, culminating in Mtf2-/- embryos dying by e15.5 due to severe anemia. Gene regulatory network (GRN) analysis demonstrated Mtf2 directly regulates Wnt signaling in erythroblasts, leading to activated canonical Wnt signaling in Mtf2-deficient erythroblasts, while chemical inhibition of canonical Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro. Using a combination of in vitro, in vivo and systems analyses, we demonstrate that Mtf2 is a critical epigenetic regulator of Wnt signaling during erythropoiesis and recast the role of polycomb accessory proteins in a tissue-specific context.

2018-07-26 | GSE72287 | GEO

MTF2 recruits Polycomb Repressive Complex 2 by helical shape-selective DNA binding

Project description:Polycomb repression of gene expression is essential for development, with a pivotal role played by trimethylation of histone H3 lysine 27 (H3K27me3) that is deposited by Polycomb Repressive Complex 2 (PRC2). The mechanism by which PRC2 is recruited to target genes has remained largely elusive, in particular in vertebrates. Here we demonstrate that MTF2, one of the three vertebrate homologs of Drosophila Polycomblike, is a DNA-binding, methylation-sensitive PRC2 recruiter in mouse embryonic stem cells. MTF2 directly binds to DNA and is essential for recruitment of PRC2 both in vitro and in vivo. Genome-wide recruitment of the PRC2 catalytic subunit EZH2 is abrogated in MTF2 knock-out cells, resulting in largely reduced H3K27me3 deposition. MTF2 selectively binds regions with a high density of unmethylated CpGs in a context of reduced helix twist, which distinguishes target from non-target CpG islands. These results demonstrate instructive recruitment of PRC2 to genomic targets by MTF2.

2018-04-09 | GSE94300 | GEO

Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis [RNA-Seq]

Project description:Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2-/- erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions. The resulting de-repression of transcriptional and signaling networks blocks definitive erythroid development, culminating in Mtf2-/- embryos dying by e15.5 due to severe anemia. Gene regulatory network (GRN) analysis demonstrated Mtf2 directly regulates Wnt signaling in erythroblasts, leading to activated canonical Wnt signaling in Mtf2-deficient erythroblasts, while chemical inhibition of canonical Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro. Using a combination of in vitro, in vivo and systems analyses, we demonstrate that Mtf2 is a critical epigenetic regulator of Wnt signaling during erythropoiesis and recast the role of polycomb accessory proteins in a tissue-specific context.

2018-07-26 | GSE72286 | GEO

Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy

Project description:This SuperSeries is composed of the SubSeries listed below. Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2- deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft (PDX) mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.

2018-07-31 | GSE98380 | GEO

Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy [ChIP-Seq]

Project description:Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2- deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft (PDX) mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.

2018-07-31 | GSE98378 | GEO

Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy [RNA-Seq]

2018-07-31 | GSE98343 | GEO

MTF2 and JARID2 function in ESC differentiation

Project description:MTF2 and JARID2 function in ESC differentiation

| PRJNA656285 | ENA

Alternative splicing signatures in apoptosis related genes of human HeLa cells with RNAi targeting p68 RNA helicase-DDX5

Project description:Alternative splicing profiling of apopotosis related genes in human HeLa cells (cervical cancer cell line) transfected with a plasmid expressing shRNAs targetting p68 helicase (DDX5, DEAD (Asp-Glu-Ala-Asp) box polypeptide 5) cloned into the pSuper expression vector compared to empty vector. Keywords: treated vs. untreated comparison; alternative splicing

2011-01-21 | GSE20010 | GEO

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